Pathogenesis of nontypeable Haemophilus influenzae infections in chronic suppurative lung disease

Abstract

The respiratory tract antimicrobial defense system is a multilayered defense mechanism that relies upon mucociliary clearance and components of both the innate and adaptive immune systems to protect the lungs from inhaled or aspirated microorganisms. One of these potential pathogens, nontypeable Haemophilus influenzae (NTHi), adopts several, multifaceted redundant strategies to successfully colonize the lower airways and establish a persistent infection. NTHi can impair mucociliary clearance, express multiple multifunctional adhesins for various cell types within the respiratory tract and evade host defenses by surviving within and between cells, forming biofilms, increasing antigenic drift, secreting proteases and antioxidants, and by host‐pathogen cross‐talk, impair macrophage and neutrophil function. NTHi is recognized as an important pathogen in several chronic lower respiratory disorders, such as protracted bacterial bronchitis, bronchiectasis, cystic fibrosis, and primary ciliary dyskinesia. The persistence of NTHi in human airways, including its capacity to form biofilms, results in chronic infection and inflammation, which can ultimately injure airway wall structures. The complex nature of the molecular pathogenetic mechanisms employed by NTHi is incompletely understood but improved understanding of its pathobiology will be important for developing effective therapies and vaccines, especially given the marked genetic heterogeneity of NTHi and its possession of phase‐variable genes. Currently, no vaccine candidates are ready for large phase III clinical trials.

Time to re-set our thinking about airways disease: lessons from history, the resurgence of chronic bronchitis / PBB and modern concepts in microbiology

“…An acute exacerbation, often triggered by a viral infection, appears to be associated with the release of planktonic bacteria, which are much more susceptible to antibiotics and hence symptoms will start to regress towards the baseline, but eliminating infection and symptoms is a much greater challenge. There appears to be a disconnection between the work being undertaken to understand more about the pulmonary microbiome and the mechanisms utilised by bacteria such as NTHi to effectively invade and persist in a niche normally protected from such disruptions (226) and the focus of many clinicians on lung function at the expense of exploring the role of chronic bacterial bronchitis as reflected in the GOLD guidelines. The lack of recognition that there is indeed a problem prevents the development of crucial clinical studies regarding the approach to treatment especially in adults.…”

“…There appears to be a disconnection between the work being undertaken to understand more about the pulmonary microbiome and the mechanisms utilised by bacteria such as NTHi to effectively invade and persist in a niche normally protected from such disruptions ( 226 ) and the focus of many clinicians on lung function at the expense of exploring the role of chronic bacterial bronchitis as reflected in the GOLD guidelines. The lack of recognition that there is indeed a problem prevents the development of crucial clinical studies regarding the approach to treatment especially in adults.…”

A Global Review of Invasive Haemophilus influenzae Disease from 2000-2023: Current Status, Challenges and Future Perspectives

“…Known to inhabit the nasopharynx and oropharynx of healthy people, it is a pathogen that only affects humans and can cause severe invasive illness [3,4].They are restricted human pathogens that include H. influenzae strains classified encapsulated (a-f) and unencapsulated or non-typeable (NTHi). The genetically varied NTHi strain can invade the nasopharynx and cause local mucosal infections, while encapsulated serotypes can also result in invasive illness [5,6]. In contrast, non-type b H. influenzae typically causes opportunistic infections.…”